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Pharmaceutical Research

, Volume 27, Issue 7, pp 1309–1317 | Cite as

Multivariate Data Analysis of Factors Affecting the In Vitro Dissolution Rate and the Apparent Solubility for a Model Basic Drug Substance in Aqueous Media

  • Anita Maria Persson
  • Curt Pettersson
  • Josefin Rosén
Research Paper

ABSTRACT

Purpose

To evaluate the usefulness of a miniaturized rotating disk equipment for the determination of factors influencing the in vitro dissolution rate, G, of a model basic drug substance (terfenadine) in different aqueous media, using experimental design and multivariate data analysis. The apparent solubility, S, was included in the chemometric study.

Methods

The dissolution rate was determined with a miniaturized rotating disk apparatus and the solubility by shake-flask methodology. Media were based on acetate, phosphate or maleate buffers—the latter used in fasted state simulated intestinal fluid (FaSSIF-V2). The chemometric analyses included fractional factorial design, principal component analysis (PCA) and orthogonal partial least squares (OPLS). Quantifications were made with a RP-HPLC-DAD system.

Results

The most influential factor for both G and S of terfenadine in the different media was pH. Apart from the ionic strength and sodium chloride concentration in the acetate medium, the effects of the other variables were insignificant, implying no wetting effect of the surfactants.

Conclusions

The miniaturized rotating disk equipment was suitable to use, in conjunction with the chemometric analyses, in the evaluation of the factors affecting the in vitro dissolution rate. The apparent solubility was found to be influenced by the same factors as G.

KEY WORDS

chemometrics dissolution media dissolution rate miniaturized rotating disk equipment solubility 

ABBREVIATIONS

ACN

acetonitrile

BCS

biopharmaceutical classification system

CMC

critical micelle concentration

DAD

diode array detector

DoE

design of experiments

G

in vitro dissolution rate

GI

gastrointestinal

I

ionic strength

IVIVC

in vitro/in vivo correlation

NaCl

sodium chloride

NaTC

sodium taurocholate

OPLS

orthogonal partial least squares

PCA

principal component analysis

RP-HPLC

reversed phase high-performance liquid chromatography

RSD

relative standard deviation

S

apparent solubility

TFA

trifluoroacetic acid

Notes

ACKNOWLEDGEMENTS

The authors would like to thank Walter Lindberg, AstraZeneca Mölndal, Sweden, for letting us borrow the miniaturized rotating disk equipment. Anders Sokolowski, AS Consulting Uppsala, Sweden, is thanked for all the exceptional help in the media and buffer calculations/recipes used in this study. Expressed gratitude is made to Eva M. Karlsson, Anders S. Carlsson and Anders AS. Karlsson, AstraZeneca Mölndal, Sweden, for the generous donation of the surfactants (NaTC and lecithin). Johan Gottfries, Gottfries Medicinal AB Göteborg, Sweden, is thanked for all constructive discussions of the multivariate data analysis. Financial support from the Carl Trygger Foundation, Sweden, is gratefully acknowledged.

Supplementary material

11095_2010_111_MOESM1_ESM.doc (91 kb)
Supplementary Material 1 (DOC 91 kb)

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Anita Maria Persson
    • 1
  • Curt Pettersson
    • 1
  • Josefin Rosén
    • 2
  1. 1.Division of Analytical Pharmaceutical ChemistryUppsala UniversityUppsalaSweden
  2. 2.Divison of PharmacognosyUppsala UniversityUppsalaSweden

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